Thick film compositions for making medical electrodes

ABSTRACT

The invention is directed to a conductive composition for iontophoretic electrodes comprising, based on solids: (a) 20-90% wt finely divided particles of silver, carbon, graphite and mixtures thereof; (b) 0-75% wt. finely divided particles of silver chloride; (c) 0.25-10% wt. hydrophilic polymer; and (d) 2-15% wt. hydrophobic thermoplastic polymer having a glass transition temperature (Tg)&gt;40° C. The invention is also directed to compositions wherein the binder comprises 5-15% wt. copolymer of hydrophilic and hydrophobic monomers.

FIELD OF THE INVENTION

This invention relates to an improvement in conductive polymer thickfilm compositions for making medical electrodes used in iontophoretictransdermal drug delivery devices.

BACKGROUND OF THE INVENTION

Medical electrodes are commonly used in two broad applications, namely,iontophoretic transdermal drug delivery and medical diagnostics byelectrochemical methods. In the area of iontophoretic transdermal drugdelivery, electrodes are the key elements in an electrochemical devicethat drives charged drug ions through the skin by an electrical current."Iontophoresis: Fundamentals" by O. Wong, Cygnus Therapeutic Systems,Redwood City, Calif. provides an overview of iontophoretic transdermaldrug delivery technology, and "Noninvasive Sampling of Biological Fluidsby lontophoresis" by P. Glickfeld et al., Pharmaceutical Research, Vol.6, No. 11. 1989, describes the use of iontophoretic techniques toextract biological molecules from a human body for medical diagnosis.The content of the articles are incorporated herein. In the area ofmedical diagnostics, conventional Ag/AgCl electrodes serve astransducers that convert electrochemical signals derived from the humanbody to electronic signals which measures/monitors body or organfunctions by conventional electronic instruments, such aselectrocardiograph (EKG), electroencephalograph (EEG) and blood sensors.There is a significant difference between conventional Ag/AgClelectrodes and iontophoretic electrodes. Iontophoretic electrodesundergo extensive compositional changes within the electrodes after use;while there is little change in conventional Ag/AgCl electrodes afteruse. Silver and silver/silver chloride polymer thick film (PTF) printinginks for iontophoretic electrodes having high electrode capacity areneeded to sustain long-duration (>24 hours) drug delivery. Aniontophoretic drug delivery device comprises an electrochemical cellconsisting of a donor electrode coated with a drug/hydrogel mixture, acounter electrode coated with hydrogel, and an electrical currentsupply. The electrodes are adhered to a patient's skin and then a lowelectric current, typically <0.2 miliampere/cm2 (mA/cm²) in currentdensity, is applied to the device. Charged drug species are driventhrough the skin by the electric field between the two electrodes.Accompanying the electric current, an oxidation reaction at the anodeand a reduction reaction at the cathode take place to maintain theelectrons/ions balance within the electrochemical cell. In the case ofAg/AgCl PTF electrodes, Ag is oxidized to AgCl at the anode and AgCl isreduced to Ag at the cathode. As Ag and AgCl are depleted in theelectrodes, the respective electrode potentials increase to high valueswhich may lead to harmful side reactions that render these electrodesunsuitable for further iontophoretic drug delivery and limits the fullutilization of Ag in the anode. Investigations were conducted to lookinto the causes of deficiencies in the presently known iontophoreticelectrode materials, such as a silver foil or polymer silver/silverchloride composites. When tested in an electrochemical cell, theseelectrodes were found to quickly form a thin layer of silver chloride asa result of electrochemical oxidation of silver on the anode surfacewhen an electric current passed through the cell. This insulating silverchloride layer leads to increased electrode potential and also hindersfurther electrochemical oxidation of silver, and eventually highelectrode potential renders the device unusable for drug delivery whenharmful side reactions occurs. This problem of Ag-to-AgCl conversionlimited at the electrode surface is due to the inability of the chlorideion to penetrate inside the anode. A hydrophobic electrode surface and ahydrophobic polymer binder matrix of a polymer thick film (PTF)electrode coating are the two major barriers that hinder chloride iontransport into the anode for sustaining the Ag-to-AgCl conversionthroughout the thickness of the electrode PTF coating.

Therefore choosing the proper anode and cathode materials is critical tothe success of achieving the best efficiency coupled with low cost foran iontophoretic device. U.S. Pat. No. 4,752,285 to Petelenz et al. andU.S. Pat. No. 4,747,819 to Phills et al. disclose iontophoretic deviceswith silver or lead metal anodes and silver chloride cathodes. U.S. Pat.No. 5,147,297 to Myers et al. discloses an iontophoretic device usingelectrodes composed of hydrophobic polymers, conductive fillers andchemical species, such as silver and silver chloride, capable ofundergoing oxidation-reduction reactions. However, these electrodessuffer from several deficiencies, such as: (a) difficult to assembleinto patches that can conform to the contour of human body, and (b)limited capacities to sustain the electric current for long drugdelivery duration due to the limited capacity of anode materials. U.S.Pat. No. 3,662,745 to Cosentino discloses EKG/EEG type of electrodesprepared by coating a Ag/AgCl paste containing hydrophobic andhydrophilic polymers, alumina powder, and silver and silver chloridepowders onto an electrically conductive substrate to improve electrodesensitivity for electrochemical measurements. These electrodes sufferfrom low conductivity and low capacities for sustaining an electriccurrent which is needed for a long duration in iontophoretic drugdelivery systems. U.S. Pat. No. 4,371,459 to Nazarenko et al. and U.S.Pat. Nos. 4,877,512 and 5,051,208 to Bowns et al. discloses silver andsilver/silver chloride conductive PTF compositions containinghydrophobic polymers. These Ag and Ag/AgCl conductive compositions weredeveloped for flexible circuits and EKG, EEG electrode applications, andwere found to suffer from deficiencies described above when used aselectrodes for an iontophoretic device. An attractive approach toovercome the deficiencies mentioned above is to print electrodes withconductive polymer thick film (PTF) materials on a plastic filmsubstrate to make flexible electrodes that can then be easily assembledinto convenient transdermal patches. The present invention providesconductive Ag or Ag/AgCl PTF compositions for medical electrodes whichmeet this need and the need for long-term iontophoretic drug delivery.In addition, the present invention overcomes the deficiencies inexisting iontophoretic drug delivery systems by: (a) efficientlyutilizing the oxidation-reduction species to achieve low cost, (b)obtaining high capacity for long-duration drug delivery, (c) exhibitingscreen printability, and (d) displaying good adhesion to plasticflexible film substrates.

SUMMARY OF INVENTION

The invention is directed to a conductive composition for iontophoreticelectrodes comprising, based on solids:

(a) 20-90% wt finely divided particles of silver, carbon, graphite andmixtures thereof;

(b) 0-75% wt. finely divided particles of silver chloride;

(c) 0.25-10% wt. hydrophilic polymer; and

(d) 2-15% wt. hydrophobic thermoplastic polymer having a glasstransition temperature (Tg)>40° C.

The invention is also directed to compositions wherein the binder is5-15% wt. a copolymer of hydrophilic and hydrophobic monomers.

DETAIL DESCRIPTION OF THE INVENTION

Polymer Binder

Several approaches can be used to make a binder matrix hydrophilic, orpartially hydrophilic. They include (a) a hydrophilic polymer binder,(b) a binder blend of hydrophilic and hydrophobic polymers, (c) a binderbeing a copolymer of hydrophobic and hydrophilic monomers. However, aPTF coating with a straight hydrophilic polymer as the binder has thedrawback of low coating cohesive strength and low adhesion to plasticfilm substrates when exposed to water, and therefore is not suitable foruses as iontophoretic electrodes which are always in contact with salinewater. It was found the use of a partially hydrophilic copolymer or apolymer blend as the binder for a PTF Ag/AgCl electrode compositionprovides good balance of ion transport, high electrode capacity, goodcohesive coating strength, good adhesion to a suitable substrate, suchas a poly(ethylene terephthalate) (PET) substrate. In a PTF coating witha binder of a hydrophobic/hydrophilic polymer blend, it is thehydrophobic polymer that provides the good coating cohesive strength andstrong adhesion to plastic film substrates even when exposed to salinewater. Suitable hydrophobic binder additions are thermoplastic polymerswith glass transition temperatures of (Tg)>40° C. so that coatings withgood flexibility and good coating hardness at ambient temperature can bemaintained. Suitable thermoplastic polymers are from the group of PETresins such as VITEL® resins from Goodyear Tire & Rubber Co.,poly(hydroxyether) such as UCAR® phenoxy resins available from UnionCarbide Co., acrylic resins such as ELVACITE® resins available from ICIInc., vinyl chloride resin, poly(vinylidene chloride-acrylonitrile) suchas SARAN® available from Dow Chemicals Inc., poly(styrene-acrylonitrile)such as TYRIL® resins available from Dow Chemicals Inc.,poly(styrene-butadiene-acrylonitrile) such as LUSTRAN® ABS resins fromavailable Monsanto Inc. Hydrophilic polymers suitable for the presentinvention are polymers that are water soluble or substantially solublein water. They are polymers chosen from the group of poly(vinylpyrrolidone) and poly(vinyl pyrrolidone-vinyl acetate),poly(acrylamide), poly(vinyl methyl ether), poly(ethylene oxide),poly(vinyl alcohol), poly(hydroxyalkyl methacrylate).

To make a suitable polymer blend, the hydrophilic and hydrophobicpolymer pair have to be compatible with each other to form a uniformpolymer mixture in a desirable ratio. The polymer blend has to besoluble in a desirable solvent suitable for making PTF materials. Toachieve the desirable coating properties and good ion transportcharacteristics, the suitable ratio by weight of hydrophilic polymer tohydrophobic polymer is in the range of 5/95 to 60/40, preferably in therange of 25/75 to 35/65. Too much of hydrophilic polymer in the polymerbinder tends to weaken the coating cohesive strength and adhesion toplastic film substrates. Too little hydrophilic polymer in the polymerbinder matrix tends to limit ion transport and thus electrodecapacities. To achieve good balance of coating strength and highelectrode capacity, 30-50% by volume of polymer in the PTF dry coatingis needed. Based on solids, 0.25-10% wt. hydrophilic polymer and 2-15%wt. hydrophobic thermoplastic polymer is used in the composition.

Partially hydrophilic polymer binder suitable for the present inventioncan also be a copolymer of a hydrophilic monomer and a hydrophobicmonomer. A suitable copolymer can be chosen from the group of poly(vinylchloride-hydroxypropyl methacrylate) and poly(vinyl chloride-vinylalcohol) such as UCAR® vinyl resins from Union Carbide Inc.,poly(styrene-vinyl pyrrolidone), poly(vinyl pyrrolidone vinyl acetate)from International Specialty Products Inc., acrylic polymers containingwater-soluble monomer such as hydroxyethyl methacrylate, acrylamide andmethacrylamide. Based on solids, 5-15% wt. of copolymer of hydrophilicand hydrophobic monomers are utilized in the present invention.

Organic Vehicle

The main purpose of the vehicle is to serve as a medium for dispersionof the polymer binder and electrically conductive particles,collectively called solids. Thus, the vehicle must first be a goodsolvent for the polymer so that a stable uniform dispersion of inorganicfillers in the polymer solution can be made. Secondly, the rheologicalproperties of the vehicle must be such that they lend good applicationproperties to the composition. Thirdly, the vehicle can be printed andthen dried by a conventional screen printing process.

Since hydrophilic polymers and hydrophobic polymers are not normallysoluble in the same type solvent, a solvent mixture is typically usedfor this type of polymer blend. Typically a suitable solvent mixture ischosen from the group of dibasic esters, such as DBE® solvents fromDuPont, DE, ethylene or propylene glycol monoalkyl ethers and theiracetates, such as DOWANOL® solvents from Dow Chemicals Inc., MI andARCOSOLV® solvents from Arco Chemicals Inc. PA., ketones, such asacetophenone, benzoacetone and alkyl ketones, n-methyl pyrrolidone,butyrolactone and aromatic solvents. When used in a fast drying coatingprocess, a mixture of solvent chosen from the group of ethanol orisopropanol, methyl ethyl ketone or methyl isobutyl ketone, and propylor butyl acetate solvents is suitable. These organic solvents are alsosuitable vehicles for copolymers of hydrophilic monomers and hydrophobicmonomers.

The ratio of vehicle to solids in the dispersions can vary considerablyand depends upon the manner in which the dispersion is to be applied andthe kind of vehicle used. Normally to achieve good coverage thedispersions will contain complementally, 60-90% solids and 40-10%vehicle. The compositions of the present invention may, of course, bemodified by the addition of other materials which do not affect itsbeneficial characteristics. Such formulation is well within the skill ofthe art.

The pastes are conveniently prepared on a three-roll mill. The viscosityof the pastes is typically 10-50 Pa.S (Brookfield RVT, 10 rpm, # 5spindle) at shear rate of 0.4/s when measured on a Brookfield HBTviscometer. The amount of vehicle utilized is determined by the finaldesired formulation viscosity.

Electrically conductive particles

In a Ag or Ag/AgCl iontophoretic anode, silver particles serve as theoxidizable species and the conductive filler. The silver particles usedin the anode of the present invention are finely divided particles witha preferable particle size within the range of 1 micron to 25 microns.Very fine silver powder is not efficient in forming a conductive networkfor electron conduction and also leads to undesirably high PTF pasteviscosity. On the other hand, large silver flakes leads to problems ofprinting. The loading of silver particles in the PTF coating determinesthe conductivity and the anode capacity. Typically, 20 percent or moreby volume of silver particles are needed to form a conductive network.Typically 20-90% wt. is used in the composition with the preferredsilver powder content in the range of 25-95% by weight in a Ag orAg/AgCl PTF coating. The typical ratio of Ag/AgCl is in the range of100/0 to 80/20 by weight for anode coating.

In a Ag/AgCl iontophoretic cathode, silver chloride serves as thereducible species to sustain the iontophoretic current. The silverchloride component is in powder form with a particle size in the rangeof 0.1 micron to 15 microns. Silver chloride powder, such as thosecommercially available from Colonial Metal Inc., DE, typically comes inagglomerated form and need to be dispersed in a PTF paste by millingprocesses. The amount of silver chloride in a Ag/AgCl electrode coatinghas to be balanced with the amount of polymer binder and conductiveparticles, such as Ag and graphite particles. Typically 0-75% wt. isused in the composition with the preferred amount of AgCl powder in therange of 25-75 percent by weight of solids. The typical silver to silverchloride ratio is in the range of 15/85 to 35/65 by weight for aconductive cathode coating.

In some iontophoretic drug delivery devices, the electric current can bereversed alternately so that drug can delivered by both the workingelectrode and the counter electrode. Each electrode functionsalternately as anode and cathode when each time the current polaritychanges. An Ag/AgCl paste with equal anode and cathode capacity isneeded to meet this requirement. Typically, a paste with a silver tosilver chloride weight ratio in the range of 70/30 to 65/35 provideselectrodes suitable for a reversible iontophoretic drug delivery device.

Graphite and conductive carbon particles can be used to replace orpartially replace silver particles as the conductive filler in a Ag/AgClcomposition or may partially replace Ag in a Ag composition. To form acarbon conductive network, the carbon-graphite need be >40% by volume ofthe solids with the remaining volume taken up by the inorganic Ag orAgCl and polymer binder. The preferred amount of conductive carbon andgraphite is 30-40% by weight of solids.

Silver flakes or powders often come with up to 0.5% adsorbed surfactantsto stabilize the silver particles in liquid dispersions. However,excessive surfactant can lead to a hydrophobic coating surface due tosurfactant migrating to the air surface during drying of a thick Ag/AgClcoating. A hydrophobic surface is a significant barrier for chloride iontransport and thus lowers the efficiency of the Ag-to-AgCl conversion.It is preferred that surfactant level be well below 0.2% by weight and asuitable solvent be used to minimize the formation of a hydrophobicelectrode surface caused by surfactant migration during drying. Suitablesurfactants are chosen from the group of anionic surfactants such assodium stearate, sodium oleate, long chain alkyl phosphate.

The inorganic particles are mixed with an essentially inert liquidmedium (vehicle) which a solution of polymer binder dissolved in thedesired solvent by mechanical mixing using a planetary mixer, thendispersed on a three roll mill to form a paste-like composition havingsuitable consistency and rheology for screen printing. The latter isprinted as a "thick film" on plastic film substrates such as polyesterfilm in the conventional manner.

The ratio of vehicle to solids in the dispersions can vary considerablyand depends upon the manner in which the dispersion is to be applied andthe kind of vehicle used. Normally to achieve good coverage, thedispersions will contain complementarily 60-90% solids and 40-10%vehicle, as described above. The compositions of the present inventionmay, of course, be modified by the addition of other materials which donot affect its beneficial characteristics. Such formulations is wellwithin the skill of the art. The amount of vehicle is determined by thefinal desired formulation viscosity.

The compositions of this invention can be printed onto plastic filmsubstrates either by using an automatic printer or a hand printer in theconventional manner. Preferably, automatic screen stenciling techniquesare employed, using a 200- or lower mesh screen.

Formulation and Application

In the preparation of the compositions of the present invention, theparticulate inorganic solids are mixed with the organic medium anddispersed with suitable equipment, such as three-roll mill, to form asuspension, resulting in a composition for which the viscosity will bein the range of about 15-50 pascal-seconds (Brookfield RVT, 10 rpm, #5spindle).

In the examples which follow, the formulation was carried out in thefollowing manner:

The ingredients of the paste are weighed together in a container. Thecomponents are then vigorously mixed to form a uniform blend; then theblend is passed through dispersing equipment, such as a three-roll mill,to achieve a good dispersion of particles. A Hegman gauge is used todetermine the state of dispersion of the particles in the paste. Thisinstrument consists of a channel in a block of steel that is 25 μm deep(1 mil) on one end and ramps up to zero depth at the other end. A bladeis used to draw down paste along the length of the channel. Scratchesappear in the channel where the agglomerates' diameter is greater thanthe channel depth. A satisfactory dispersion will give a fourth scratchpoint of 10-18 μm typically. The point at which half of the channel isuncovered with a well dispersed paste is between 3 and 8 μm typically.Fourth scratch measurement of >20 μm and "half-channel" measurementsof >10 μm indicate a poorly dispersed suspension.

The compositions are then applied to a substrate, such as a PETsubstrate, usually by the process of screen printing, to a dry thicknessof 100 microns depending on the drug delivery duration required". Thecompositions of this invention can be printed onto the substrates eitherby using an automatic printer or a hand printer in the conventionalmanner, preferably automatic screen printing techniques are employedusing a 60- to 165-mesh screen. The printed pattern is then dried atabout 120° C. for about 5-15 minutes.

The present invention will be described in further detail by givingpractical examples. The scope of the present invention, however, is notlimited in any way by these practical examples.

EXAMPLE 1

This example demonstrate the preparation of a Ag PTF compositioncontaining a hydrophobic/hydrophilic polymer blend suitable for use inmaking iontophoretic anode. Acrylic resin and PVP-VA resin weredissolved in dipropylene glycol methyl ether. Silver flake and silverpowder were added to the polymer solution with mixing and then milled ona 3-roll mill to a fineness reading of <5 micron as detailed above. Theresultant paste has a viscosity of "20-30Pa.S"

    ______________________________________                                        Ingredient            Percent by Weight                                       ______________________________________                                        Acrylic resin (1)     4.0                                                     PVP-VA resin (2)      1.7                                                     Dipropylene glycol methyl ether                                                                     10.5                                                    Silver flake          20.7                                                    silver powder         62.1                                                                          100.0                                                   ______________________________________                                         (1) Elvacite 2016 resin from ICI, MO                                          (2) PVPVA S630 resin from International Specialty Products, NJ           

EXAMPLE 2

This example demonstrates the preparation of a Ag/AgCl ink containing anacrylic/PVP-VA polymer blend suitable for use as an iontophoreticcathode. Paste sample was prepared in the same way as Example 1.

    ______________________________________                                        Ingredients           Percent by Weight                                       ______________________________________                                        PVP-VA resin (2)      2.5                                                     Acrylic resin (1)     5.9                                                     Dipropylene glycol methyl ether                                                                     12.2                                                    Aromatic 150          3.0                                                     Silver flake          24.8                                                    Silver chloride (3)   51.6                                                                          100.0                                                   ______________________________________                                         (3) 325 mesh AgCl powder from Colonial Metals Inc., DE                   

EXAMPLE 3

This example demonstrates the preparation of a Ag/AgCl paste with ahydrophilic/hydrophobic polymer blend suitable for use in aniontophoretic anode. Acrylic resin and PVP-VA resin were dissolved indiethyl oxalate and then Ag flakes and AgCl powder were added withmixing. The paste mixture was then milled on a 3-roll mill to a finenessreading of <5 micron. The resultant Ag paste has a viscosity of 25-30Pa.S.

    ______________________________________                                        Ingredient     Percent by Weight                                              ______________________________________                                        Acrylic resin (1)                                                                            4.17                                                           PVP-VA resin (2)                                                                             1.78                                                           Diethyl oxalate                                                                              11.05                                                          Silver flake   78.87                                                          Silver chloride                                                                              4.13                                                                          100.0                                                          ______________________________________                                    

EXAMPLE 4

This example shows a Ag PTF composition for iontophoretic anode having apartially hydrophilic copolymer as the polymeric binder. Paste samplewas prepared in the same way as Example 1.

    ______________________________________                                        Ingredient       Percent by Weight                                            ______________________________________                                        PVP-VA E335 resin (4)                                                                          6.1                                                          Diethyl oxalate  14.1                                                         Silver flake     79.8                                                                          100.0                                                        ______________________________________                                         (4) PVPVA E335 from International Specialty Products, NJ                 

EXAMPLE 5

This example shows a Ag PTF composition having a copolymer ofhydrophilic acrylic monomer and hydrophobic vinyl monomer as thepolymeric binder. Paste sample was prepared in the same way as Example1.

    ______________________________________                                        Ingredient         Percent by Weight                                          ______________________________________                                        Poly(vinyl chloride-hydroxypropyl                                                                6.7                                                        methacrylate) resin (5)                                                       N-methyl pyrrolidone                                                                             7.2                                                        Aromatic 150       12.0                                                       Silver flake       18.5                                                       Silver powder      55.6                                                                          100.0                                                      ______________________________________                                         (5) UCAR* vinyl resin VAGF resin from Union Carbide, Danbury CT          

EXAMPLE 6

This example shows a Ag/AgCl PTF composition for iontophoretic cathodeprinted on a conductive substrate. Paste sample was prepared in the sameway as Example 2.

    ______________________________________                                        Ingredient         Percent by Weight                                          ______________________________________                                        PVP-VA resin (2)   2.6                                                        Acrylic resin (1)  6.0                                                        Dipropylene glycol methyl ether                                                                  14.0                                                       Aromatic 150       3.5                                                        Silver chloride (3)                                                                              59.1                                                       Silver flake       14.8                                                                          100.0                                                      ______________________________________                                    

EXAMPLE 7

This example demonstrate a Ag/AgCl composition suitable for both cathodeand anode in a reversible iontophoretic drug delivery device. Ink samplewas prepared using the same procedure as Example 1.

    ______________________________________                                        Ingredient         Percent by Weight                                          ______________________________________                                        Acrylic resin (1)  5.13                                                       PVP-VA resin (2)   2.2                                                        Aromatic 150       2.2                                                        Dipropylene glycol methyl ether                                                                  8.8                                                        Silver flake       13.27                                                      Silver powder      39.8                                                       Silver chloride    28.6                                                                          100.0                                                      ______________________________________                                    

EXAMPLE 8

This example demonstrates the preparation of a conductive carbon andAgCl composition suitable for iontophoretic cathode.

    ______________________________________                                        Ingredient         Weight percent                                             ______________________________________                                        Phenoxy resin (6)  8.1                                                        PVP-VA resin (2)   2.7                                                        Dipropylene glycol methyl ether                                                                  22.4                                                       Aromatic 150       7.8                                                        Butyrolactone      13.0                                                       Silver chloride    25.6                                                       Conductive carbon (7)                                                                            10.2                                                       Graphite (8)       10.2                                                       Sodium stearate    0.2                                                                           100.0                                                      ______________________________________                                         (6) Phenoxy PKH from Union Carbide, CT                                        (7) VULCAN XC72R from Carbot, MA                                              (8) HPN10 graphite from Dixon Ticonderoga, NJ                            

EXAMPLE 9

A silver and carbon paste was prepared for use as an iontophoreticanode.

    ______________________________________                                        Ingredient         Weight percent                                             ______________________________________                                        Acrylic resin (1)  6.6                                                        PVP-VA resin (2)   2.8                                                        Dipropylene glycol methyl ether                                                                  33.1                                                       Conductive carbon (7)                                                                            6.3                                                        Graphite (8)       14.8                                                       Silver flake       10.2                                                       Silver powder      26.2                                                                          100.0                                                      ______________________________________                                    

EXAMPLE 10 COMPARATIVE

A silver PTF paste containing a hydrophobic phenoxy resin was preparedin the same manner as in Example 1 with the composition shown below. Theink sample was printed and tested as an iontophoretic anode.

    ______________________________________                                        Ingredient         Percent by Weight                                          ______________________________________                                        Phenoxy resin (6)  5.9                                                        Dipropylene glycol methyl ether                                                                  24.1                                                       Silver flake       70.0                                                                          100.0                                                      ______________________________________                                    

EXAMPLE 11 COMPARATIVE

A PTF paste containing a silver/silver chloride and hydrophobic PETresin was prepared in the same way as Example 1 and then tested as aniontophoretic anode.

    ______________________________________                                        Ingredient         Percent by Weight                                          ______________________________________                                        Acrylic resin (9)  9.2                                                        Propylene glycol methyl acetate                                                                  8.9                                                        Ethylene glycol butyl acetate                                                                    11.9                                                       Silver flake       70.0                                                                          100.0                                                      ______________________________________                                         (9) Acryloid A11 from RohmHaas, PA                                       

ELECTRODE TESTINGS

A Ag or Ag/AgCl PTF composition is typically screen printed on a PETfilm substrate to a targeted coat weight using wire mesh screen of165-60 mesh. For Example 6, the Ag/AgCl coating was printed on aconductive carbon coating on a PET substrate. The dried coating was thentested as an anode or a cathode in an electrochemical test cell. Thetest cell consists of a 0.9% NaCl solution (saline water), a testelectrode with 1 cm² submerged in the saline water and a counterelectrode having a known electrode capacity of >100miliampere.minutes/cm² (mA.min./cm2) with 6 cm² submerged in the salinewater. A power supply and a chart recorder were connected to the twoelectrodes. During testing, a constant current, typically at 0.5 mA, wasapplied to the two electrodes, and the voltage across the two electrodeswas recorded vs time on a chart recorder. The test was stopped when thevoltage reached one volt at which electrolysis of water becamesignificant rendering further iontophoretic drug delivery undesirable.The electrode capacity of a test electrode, measured in unit ofmA.min./cm², is calculated by multiplying the recorded time in minute by0.5 mA/cm2. Typical capacity for Ag and AgCl PTF examples describedabove are listed below. For comparison, a typical iontophoretic deviceoperating at a current density of 0.1 mA/cm2 requires a electrodecapacity of 144 mA.min./cm2 for both cathode and anode to sustain a24-hour drug delivery.

    ______________________________________                                                 Coat Weight    Electrode Capacity                                    Example  (gm/cm.sup.2)  (mA.min./cm.sup.2)                                    ______________________________________                                                          Anode Cathode                                               1        59.8           560     --                                            2        23.7           --      222                                           3        31.4           170     --                                            4        10.3           70      --                                            5        19.2           53      --                                            6        7.1            --      58                                            7        30.8           188     230                                           8        7.9            --      33                                            9        13             70      --                                            10       16.8           4       --                                            11       21.7           3       --                                            ______________________________________                                    

What is claimed is:
 1. A conductive composition for iontophoreticelectrodes comprising, based on solids:(a) 20-90% wt. of silverparticles; (b) 0-75% wt. of silver chloride particles; (c) 0.25-10% wt.hydrophilic polymer; and (d) 2-15% wt. hydrophobic thermoplastic polymerhaving a Tg above 40° C. said conductive composition further comprisinga vehicle consisting of organic solvent or organic solvent mixtures. 2.The composition of claim 1 wherein the hydrophilic polymer is selectedfrom the group consisting of poly(vinylpyrrolidone),poly(vinylpyrrolidone-vinyl acetate), poly(vinyl methyl ether),poly(ethylene oxide), poly(vinyl alcohol), poly(acrylamide), andpoly(hydroxyalkyl methacrylate).
 3. The composition of claim 1 whereinthe hydrophobic polymer is selected from the group consisting of acrylicpolymer, polyhydroxyether, poly(styrene-acrylonitrile), poly(vinylidenechloride-acrylonitrile), polyester,poly(acrylonitrile-butadiene-styrene).
 4. The composition in claim 1wherein the silver particles are in the range of 1-25 microns.
 5. Thecomposition in claim 1 wherein the silver chloride particles are in therange of 0.1-15 microns.
 6. The composition in claim 1 furthercomprising conductive fillers selective from the group consisting ofcarbon and graphite.
 7. The composition in claim 1 wherein the organicvehicle is selected from the group consisting of alkyl ketones, aromaticketones, glycol alkyl ethers and their acetates, dibasic esters,n-methylpyrrolidone, butyrolactone, and aromatic solvents.
 8. Thecomposition of claim 1 wherein silver to silver chloride ratio is in therange of 100/0 to 80/20 by weight for iontophoretic anode.
 9. Thecomposition of claim 1 wherein silver to silver chloride ratio is in therange of 15/85 to 35/65 by weight for iontophoretic cathode.
 10. Thecomposition of claim 1 wherein the silver to silver chloride ratio byweight is in the range of 70/30 to 65/35.